Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease where the lungs become fibrotic and the patient struggles to breathe. IPF has a 5-year survival of rate of 30-50% and limited treatment options. It is believed that IPF develops from repeated alveolar injuries, leading to persistent signals for fibroblast activation, proliferation, and differentiation to myofibroblasts. The Food and Drug Administration has approved the drugs, pirfenidone (ESBRIET®) and nintedanib (OFEV® and GARGATEF®), for IPF treatment; however, despite the benefits these drugs can provide in improving quality of life, patients still experience precipitous drops in their respiratory function and high mortality rates.
FK506 or fujimycin (TACROLIMUS®) is a macrolide antibiotic that is currently being used for immunosuppression. It is believed to act principally through impairment of gene expression in target cells. For example, FK506 can bond to an immunophilin, FK506 binding protein. FK506 also has anti-fibrotic properties, but its immunosuppression properties can prevent it from being used as an anti-fibrotic. The challenge is to make an anti-fibrotic drug that does not cause immunosuppression.
Additionally, tau aggregation is a commonly observed event in many neurodegenerative disorders. Recent clinical and biochemical research has suggested that one of the protein chaperones, FKBP52, may play a role in certain types of tauopathy. However, limited chemical probes are available to study the function of this protein.
Therefore, there is a need for new compositions and methods that can be used to treat idiopathic pulmonary fibrosis and/or tauopathy.